Glembatumumab vedotin 10-2016 - pharmastore.informa.com · 9 Figure 1: Glembatumumab vedotin for...

Glembatumumab vedotin Product Analysis

Ref Code: DMKC0159162Publication Date: 15/04/2016Author: David Dahan

Datamonitor HealthcarePharma intelligence |


2

glembatumumab vedotin Product Analysis DMKC0159162 | Published on 15/04/2016

© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed

2

Reference: DMKC0159162 First published: 15/04/2016

About Datamonitor Healthcare Bringing you a clearer, richer and more responsive view of the pharma & healthcare market.

Complete market coverage Our independent research and analysis provides extensive coverage of major disease areas, companies and strategic issues,giving you the perspective to identify opportunities and threats arising from shifting market dynamics and the insights torespond with faster, more effective decision-making.

Unique expert capabilities With teams located across developed and emerging pharma markets, we are uniquely placed to understand localhealthcare trends and provide accurate and reliable recommendations. By working closely with our partners at MedTrack,Citeline, SCRIP Intelligence and Informa Healthcare, our experts are able to share data and resources to produce the mostauthoritative and robust market intelligence. With over 700 clients across the pharma and biotech industries, we are reliedupon to provide strategic guidance, not only through published analysis, but also tailored support solutions.

Cutting-edge delivery Available through single reports or via subscription to our state-of-the art online intelligence service that featuresintuitive design and interactive capabilities, our analysis offers the definitive platform to enhance your productmanagement, market assessment and strategic planning.

Contact Us For more information about our products or to arrange a demo of the our online service, please contact:[email protected]

Disclaimer All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means,electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, DatamonitorHealthcare. The facts of this report are believed to be correct at the time of publication but cannot be guaranteed. Pleasenote that the findings, conclusions and recommendations that Datamonitor Healthcare delivers will be based oninformation gathered in good faith from both primary and secondary sources, whose accuracy we are not always in aposition to guarantee. As such, Datamonitor Healthcare can accept no liability whatsoever for actions taken based on anyinformation that may subsequently prove to be incorrect. For more information about our products or to arrange a demonstration of the our online service, please contact:[email protected]


3



3

TABLE OF CONTENTS

LIST OF FIGURES

LIST OF TABLES

4 PRODUCT PROFILES4 glembatumumab vedotin : Breast cancer: triple-negative

9 Figure 1: Glembatumumab vedotin for triple-negative breast cancer – SWOT analysis9 Figure 2: Datamonitor Healthcare's drug assessment summary of glembatumumab vedotin for

triple-negative breast cancer10 Figure 3: Datamonitor Healthcare's drug assessment summary of glembatumumab vedotin for

triple-negative breast cancer

4 Table 1: Glembatumumab vedotin drug profile5 Table 2: Glembatumumab vedotin Phase IIb trial in triple-negative breast cancer7 Table 3: Glembatumumab vedotin Phase IIb data in triple-negative breast cancer


4



4

PRODUCT PROFILES glembatumumab vedotin : Breast cancer: triple-negative PRODUCT PROFILE Analyst Outlook

Glembatumumab vedotin (Celldex) is positioned to be the first antibody–drug conjugate approved fortriple-negative breast cancer (TNBC). It is currently in a Phase II registration trial where it is beingassessed as a first-, second-, or third-line treatment in metastatic TNBC patients overexpressing thetransmembrane glycoprotein non-metastatic B (GPNMB). As an antibody–drug conjugate,glembatumumab vedotin could have a better safety profile than the chemotherapeutics currentlybeing used in metastatic TNBC. Glembatumumab vedotin will be restricted to the subpopulation ofTNBC patients that overexpress the GPNMB target; however, it is not yet clear how big this patientgroup will be. Drug Overview

Glembatumumab vedotin is an antibody–drug conjugate that targets cancer cells expressing GPNMB.This fully human monoclonal antibody is linked to monomethyl auristatin E (MMAE), a potent,peptide-derived antimitotic drug which targets microtubules and which is too toxic to be used as amonotherapy. Glembatumumab vedotin uses a valine-citrulline enzyme cleavable linker that is stablein the bloodstream. Once the drug is internalized into the cell, MMAE is released and inducesapoptosis.


5



5

DEVELOPMENT OVERVIEW

Glembatumumab vedotin is an antibody–drug conjugate developed by Celldex. It is currently beinginvestigated in METRIC, a Phase IIb trial for patients with metastatic GPNMB-overexpressing TNBC(ClinicalTrials.gov identifier: NCT01997333). In May 2010, the US Food and Drug Administrationgranted fast track designation to glembatumumab vedotin for the treatment of advancedrefractory/resistant GPNMB-expressing breast cancer.

The table below summarizes the design of the Phase IIb registration study.

Table 1: Glembatumumab vedotin drug profile

Molecule glembatumumab vedotin

Phase of development Phase IIb

Mechanism of action Tubulin inhibitor

Originator Celldex

Marketing company Celldex

Targeted indication Metastatic GPNMB-overexpressing TNBC

Formulation Intravenous infusion

Pricing strategy $9,800 per month (based on Kadcyla)

Dosing frequency Administered on day 1 of each 21-day cycle

Estimated approval date Q3 2017 (US, 5EU), Q3 2020 (Japan)

Alternative names CDX-011, CR011-vcMMAE, CR-011-vcMMAE, CR011, glemba

5EU = five major EU markets (France, Germany, Italy, Spain, and the UK); TNBC = triple-negative breast cancer; GPNMP = glycoprotein non-

metastatic B

Source: Datamonitor Healthcare; Biomedtracker; Medtrack; Pharmaprojects; ClinicalTrials.gov


6



6

An overview of early-phase data for glembatumumab vedotin in TNBC is summarized in the tablebelow.

Table 2: Glembatumumab vedotin Phase IIb trial in triple-negative breast cancer

Trial Sample size Target patients Study design Treatment arms Primary

endpoints

Start

date/primary

completion date

METRIC

(NCT01997333)

(Phase IIb)

300 Metastatic

GPNMB-

overexpressing

TNBC

I, R, ES, PA, OL, T Arm 1:

glembatumumab

vedotin IV infusion

on day 1 of each

21-day cycle

Arm 2:

capecitabine on

days 1–14 of each

21-day cycle

PFS December

2013/September

2016

ES = efficacy/safety; GPNMB = glycoprotein non-metastatic B; I = interventional; IV = intravenous; OL = open-label; PA = parallel-

assignment; PFS = progression-free survival; R = randomized; T = treatment; TNBC = triple-negative breast cancer

Source: Biomedtracker; ClinicalTrials.gov


7



7

Table 3: Glembatumumab vedotin Phase IIb data in triple-negative breast cancer

Phase Sample size Target patients Dosing tested and duration Results Reference

EMERGE

(Phase IIb)

124 GPNMB-expressing, advanced,

heavily pretreated breast cancer

Arm 1: glembatumumab vedotin

(1.88mg/kg) administered as an

intravenous infusion on Day 1 of

each 21-day cycle

Arm 2: IC single-agent

chemotherapy

All patients:

Arm 1: ORR = 6%

Arm 2: ORR = 7%;

High GPNMB expression patients:

Arm 1 (n = 23):

ORR = 30%

PFS = 2.8 months

OS = 10.0 months

Arm 2 (n = 11):

ORR = 9%

PFS = 1.5 months

OS = 5.7 months;

TNBC & high GPNMB expression

Yardley et al., 2015


8



8

Table 3: Glembatumumab vedotin Phase IIb data in triple-negative breast cancer

Phase Sample size Target patients Dosing tested and duration Results Reference

Arm 1 (n = 10):

ORR = 40%

PFS = 3.5 months

OS = 10.0 months

Arm 2 (n=6):

ORR = 0%

PFS = 1.5 months

OS = 5.5 months

GPNMB = glycoprotein non-metastatic B; IC = investigator’s choice; ORR = overall response rate; OS = overall survival; PFS = progression-free survival; TNBC = triple-negative breast cancer

Source: see above


9



9

SWOT ANALYSIS

CLINICAL AND COMMERCIAL ATTRACTIVENESS

The figure below depicts Datamonitor Healthcare’s drug assessment summary for glembatumumabvedotin in TNBC.

Figure 1: Glembatumumab vedotin for triple-negative breast cancer – SWOT analysis

Source: Datamonitor Healthcare


10



10

The figure below provides a breakdown of how Datamonitor Healthcare scored glembatumumabvedotin’s clinical and commercial attractiveness. The weighting given to each attribute is also shown.Abraxane (albumin-bound paclitaxel; Celgene/Taiho) was used as the comparator drug.

Figure 2: Datamonitor Healthcare's drug assessment summary of glembatumumab vedotin for triple-negative breastcancer



11



11

Glembatumumab vedotin is positioned to be the first antibody–drug conjugate approvedfor TNBC

Glembatumumab vedotin is positioned to be the first antibody–drug conjugate approved for TNBC. Itis currently in a Phase II registration trial where it is being assessed as a first-, second-, or third-linetreatment in metastatic TNBC patients expressing GPNMB. The Phase IIb EMERGE study showed animpressive doubling in overall survival in TNBC patients with high GPNMB expression (5.5 months forinvestigator’s choice chemotherapy versus 10.0 months with glembatumumab vedotin: n=6 and n=10,respectively). These patients were heavily pretreated with 2–7 lines of prior chemotherapy.Glembatumumab vedotin was found to be well tolerated in this patient group, and the most commontreatment-related adverse events were nausea, rash, fatigue, neuropathy, alopecia, and neutropenia.As an antibody–drug conjugate, glembatumumab vedotin is likely to have a better safety profile thanthe chemotherapeutics currently being used in metastatic TNBC. Glembatumumab vedotin will target a subpopulation of TNBC patients

Glembatumumab will be used as a targeted therapy for the treatment of TNBC but it is uncertain howbig its target population will be. In the Phase IIb EMERGE study, 99% of TNBC patients that wereassessed met the enrollment criteria of GPNMB expression in ≥5% of cells. However, optimal resultswere seen in a subpopulation of TNBC patients that had expression of GPNMB in >25% of malignantepithelial cells. It is not yet clear what percentage of TNBC patients fall in this high GPNMBexpression group. The registration trial is enrolling TNBC patients that overexpress GPNMB, which is

Figure 3: Datamonitor Healthcare's drug assessment summary of glembatumumab vedotin for triple-negative breastcancer



12



12

likely to correspond to the higher 25% threshold. Combination with Gleevec could allow glembatumumab vedotin to access a largerpopulation of TNBC patients

Preclinical data has shown that the tyrosine kinase inhibitor Gleevec (imatinib; Novartis) increasedGPNMB expression by western blot in both melanoma and glioblastoma cell lines (Qian et al., 2008). Itis therefore feasible that a combination therapy of glembatumumab vedotin and Gleevec couldincrease the target population for this therapy in TNBC by boosting the number of malignant cellsexpressing GPNMB. However, no trial looking at this combination has been announced to date. Bibliography

Qian X, Mills E, Torgov M, LaRochelle WJ, Jeffers M (2008) Pharmacologically enhanced expression ofGPNMB increases the sensitivity of melanoma cells to the CR011-vcMMAE antibody-drug conjugate.Molecular Oncology, 2(1), 81–93 <DOI>10.1016/j.molonc.2008.02.002</DOI>.

Yardley DA, Weaver R, Melisko ME, Saleh MN, Arena FP, et al. (2015) EMERGE: A Randomized Phase IIStudy of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced GlycoproteinNMB–Expressing Breast Cancer. Journal of Clinical Oncology, 33(14), 1609–19<PMID>25847941</PMID>.

Date post:	12-Sep-2019
Category:	Documents
Upload:	others
View:	2 times
Download:	0 times

Glembatumumab vedotin 10-2016 - pharmastore.informa.com · 9 Figure 1: Glembatumumab vedotin for...

Documents